Subarachnoid haemorrhage induced proliferation of leptomeningeal cells and deposition of extracellular matrices in the arachnoid granulations and subarachnoid space. Immunhistochemical study

Subarachnoid haemorrhage (SAH) often leads to subarachnoid fibrosis and resultant normal pressure hydrocephalus; however, how subarachnoid fibrosis occurs is unknown. We examined the changes within arachnoid granulations (AGs) and the subarachnoid space (SAS) chronologically at the parasagittal region obtained from patients with SAH at autopsy and made comparison with controls by immunostaining for cytokeratin, specific marker for leptomeningeal cells and by the elastica Masson-Goldner methods. Within a week some AGs were torn, and many inflammatory cells filled the AGs and SAS. Cytokeratin positive cells were scarce. During the next two weeks cytokeratin positive cells increased. After three weeks, AGs and SAS were filled by dense deposits of extracellular matrices surrounded by multiple layers of leptomeningeal cells.     

Hemocompatibility in hemodialysis and erythropoietin therapy

Two studies designed to investigate the effect of recombinant human erythropoietin (rHuEPO) treatment of anemia in chronic dialysis patients on hemocompatibility were conducted. Study 1, whose main aim was to establish whether treatment with rHuEPO enhances coagulation activation during dialysis, included 15 patients before rHuEPO therapy at a mean hematocrit (HCT) of 22.3% and then during therapy at a HCT of 29.3%. The plasma concentrations of the thrombin-antithrombin III complex were not higher during rHuEPO therapy than before it when performing hemodialysis with a Cuprophan membrane. No significant difference was demonstrated either in the values of activated clotting times (Hemochron), thrombocyte or white blood cell counts (Coulter S+II), or in plasma C5a concentrations (ELISA) established during dialysis sessions before and during rHuEPO therapy. In Study 2, which focused primarily on the question of whether or not rHuEPO therapy increases thrombocyte activation during hemodialysis, 8 patients on chronic dialysis were examined both before therapy at a mean HCT value of 22.1% and during rHuEPO therapy at a HCT of 31.5%, invariably during dialysis with either a Cuprophan or polyacrylonitrile (AN69HF) membrane. The plasma concentrations of beta-thromboglobulin (ELISA) did not differ between the examinations made during rHuEPO and before rHuEPO therapy; however, statistically significant differences were found between dialysis sessions involving Cuprophan and AN69HF membranes. No significant difference between examination before and during rHuEPO was demonstrated in activated clotting time nor thrombocyte and white blood cell counts in this study either. The authors conclude that rHuEPO therapy does not enhance coagulation activation during hemodialysis, does not have an effect on thrombocyte activation, and does not influence complement activation and changes in white blood cell counts.     

Percutaneous lumbar nucleotomy

The nature of the events whereby the reactive intermediates resulting from the bioactivation of bromobenzene and furosemide induce hepatotoxicity is unknown. To examine a role for disturbances in intracellular calcium homeostasis, secondary to a depletion in cellular reduced glutathione (GSH) and reduced protein thiols (PSHs), isolated mouse hepatocytes were exposed to cytotoxic concentrations of bromobenzene or furosemide. Cytosolic calcium concentration, as well as thiol status, was determined. The incubation of hepatocytes with 3.0 mM bromobenzene, and subsequent additions (1.2 mM) of the agent every hour, resulted in significant GSH depletion. The loss of plasma membrane integrity at 1.5 h preceded both a rise in the cytosolic Ca2+ concentration and depletion of total PSH content. Furosemide (1.0 mM) produced a 70% depletion in cellular GSH content in isolated hepatocytes. The initiation of cell damage occurred concurrently with both a rise in the cytosolic Ca2+ concentration and a depletion of total PSH content 4 h following furosemide addition. Since the increase in cytosolic Ca2+ did not precede cytotoxicity, these results do not support an initiating role for Ca2+ deregulation in bromobenzene and furosemide hepatotoxicities. In addition, depletion of PSH content did not correlate with bromobenzene- or furosemide-induced cytotoxicity.     

Hyaluronic acid induced hyaluronic acid binding protein phosphorylation and inositol triphosphate formation in lymphocytes

In this report, the role of 34 kDa HA-binding protein in hyaluronic acid-induced cellular signalling in lymphocytes has been examined. The binding of 125I-HA to lymphocytes in vivo was found to be inhibited by pre-incubation of the cells with anti-34 kDa HA-binding protein antibodies, thus confirming 34 kDa HA-binding protein as the specific HA-receptor in lymphocytes. This observation was substantiated by anti-34 kDa HA-binding protein antibodies immunoblotting and 125I-HA ligand blotting of lymphocytes cell lysate. The HA-induced cell aggregation, tyrosine phosphorylation and cytoskeletal protein phosphorylation demonstrate the HA-induced early cellular signalling events in lymphocytes. Further, to study the involvement of 34 kDa HA-binding protein in mitogen induced lymphocyte signalling, we studied in vivo phosphorylation and secondary messenger formation. The enhanced 34 kDa HA-binding protein phosphorylation by HA and the inhibition of cellular aggregation and IP3 formation by anti-HA-binding protein antibodies revealed that 34 kDa HA-binding protein is one of the potential mediators in HA-induced signal transduction.     

Cytomegalovirus disease accompanied by severe hypoproteinemia in a patient with adult T-cell leukemia-lymphoma

A 62-year-old Japanese man complained of fever, general fatigue, anorexia and watery diarrhea during remission of adult T-cell leukemia-lymphoma. Laboratory examinations showed severe hypoproteinemia (2.9 g/dl). However, neither intestinal lesions associated with ATL nor findings suggesting protein losing gastroenteropathy were observed. Cytomegalovirus (CMV) antigen detection assay using peripheral blood leukocytes revealed that he had an active CMV infection with hemophagocytic syndrome. Treatment with ganciclovir and methylprednisolone led to an improvement of hypoproteinemia. CMV disease and associated hemophagocytic syndrome should be considered as a cause of hypoproteinemia in an immunocompromised host.